Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

A series of 22 derivatives of AZT substituted at the N-3 position of the thymine base were prepared and evaluated for anti-HIV activity in cell culture (Lai strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent displayed activities in the 0.045−0.082 μM range. The analogs 12d, 12e, 12q, 15, and 19 were active at